BACKGROUND: Post-operative pain management is usually limited by adverse effects such as nausea and vomiting. Adjuvant treatment with an inexpensive opioid-sparing drug such as ketamine may be of value in giving better analgesia with fewer adverse effects. The objective of this systematic review was to evaluate the effectiveness and tolerability of ketamine administered peri-operatively in the treatment of acute post-operative pain in adults. METHODS: Studies were identified from MEDLINE (1966-2004), EMBASE (1980-2004), the Cochrane Library (2004) and by hand searching reference lists from review articles and trials. The manufacturer of ketamine (Pfizer AS, Lysaker, Norway) provided search results from their in-house database, PARDLARS. Randomized and controlled trials (RCTs) of adult patients undergoing surgery, being treated with peri-operative ketamine, placebo or an active control were considered for inclusion. RESULTS: Eighteen trials were excluded. Thirty-seven trials were included. Twenty-seven out of 37 trials found that peri-operative ketamine reduced rescue analgesic requirements or pain intensity, or both. Quantitative analysis showed that treatment with ketamine reduced 24-h patient-controlled analgesia (PCA) morphine consumption and post-operative nausea and vomiting (PONV). Adverse effects were mild or absent. CONCLUSION: In the first 24 h after surgery, ketamine reduces morphine requirements. Ketamine also reduces PONV. Adverse effects are mild or absent. These data should be interpreted with caution as the retrieved studies were heterogenous and the result of the meta-analysis can not be translated into any specific administration regimen with ketamine.